Angiotensinases restrict locally generated angiotensin II to the blood vessel wall.
We tested the hypothesis that angiotensinases limit the spillover of locally formed angiotensin II into the circulation. The release of angiotensin peptides from isolated rat hindquarters perfused with an artificial medium was measured by high-performance liquid chromatography and radioimmunoassay. The spontaneous release of angiotensins was increased by the angiotensinase inhibitors phenanthroline (850+/-195 versus 95+/-33 fmol of angiotensin I per 30 minutes in controls, P<.05, n=5 each) and amastatin (P<.05, n=5 each). Infusion of renin induced sustained local angiotensin I formation, which was also increased by phenanthroline. Stimulation of local angiotensin formation by renin infusion was compared with infusion of exogenous angiotensin II. Renin caused similar increases of perfusion pressure (11.1+/-2.2 versus 7.6+/-1.9 mm Hg after angiotensin II, P>.05) despite lower angiotensin II levels in the venous effluent than during infusion of exogenous angiotensin II (65+/-2 versus 482+/-33 fmol/mL, P<.05, n=7 each). Thus, renin must have caused higher angiotensin II tissue levels than indicated by the measurements in the venous effluent. The pressor response to renin was abolished by the type 1 angiotensin II receptor antagonist losartan. We conclude that the major part of locally generated angiotensins is not released into the circulation but degraded by angiotensinases within the tissue compartment.
Hilgers
K F
KF
Department of Medicine IV, University of Erlangen, Germany. mfm435@rzmail.uni-erlangen.de
Bingener
E
E
Stumpf
C
C
Müller
D N
DN
Schmieder
R E
RE
Veelken
R
R
D000803:Angiotensin I / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D010450:Endopeptidases / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D007700:Kinetics; D008297:Male; D010618:Phenanthrolines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000494:pharmacology
D010618:Phenanthrolines; D011480:Protease Inhibitors; C076819:angiotensinase; D000804:Angiotensin II; D000803:Angiotensin I; D010450:Endopeptidases; D012083:Renin